The overall objective of this Fast-Track proposal is to develop and evaluate a novel, neuroscience-based multimedia training program for the treatment of cognitive deficits in schizophrenia. Neurocognitive deficits are a core feature of schizophrenia, and inhibit schizophrenics' ability to participate in rehabilitation programs, maintain social relationships, gain and maintain employment, and function independently in the community. An intervention that substantively improved schizophrenics' cognitive functioning could reduce the negative sequelae of this illness. A rapidly growing body of evidence from the neuroscience of developmental and adult brain plasticity has led to increased understanding of the neurological bases of learning and memory, and supported a specific disease-origin model of schizophrenia. We propose to develop an intensive, neuroscience-based multimedia intervention, rooted in this new disease-origin model, to ameliorate cognitive functioning and symptom expression in schizophrenia. A preliminary, incomplete form of the proposed multimedia training program has been evaluated in a pilot study with 13 schizophrenics. This training significantly ameliorated important neurocognitive deficits in most subjects, improved cognitive functioning in areas that were not targeted in training, and reduced positive psychotic symptoms. Based on these findings, we propose to create a revised and expanded training program to more directly, completely, and powerfully address a broader range of neurocognitive impairments predictive of functional outcomes in schizophrenia. We have already developed 2 of the 3 modules that will comprise the training program. Phase I of this Fast- Track proposal aims to support the development of a critical third training module targeting associative and executive cognitive processes, and to obtain feasibility and acceptability data to inform program revisions. In Phase II, we will conduct a randomized, controlled trial to evaluate the neurological and broader clinical impact of this innovative therapeutic product. This self-administered, computer-based therapy could be marketed worldwide to health care professionals who treat schizophrenics, and to families who care for them.